Follicle Atresia Is Regulated by Fibroblast Growth Factor-18 in Cattle.
Bibliographic record
Abstract
Understanding the paracrine events that regulate fertility in the cow is necessary not only because of the agricultural importance of this species, but also its potential use as a model for humans. Fibroblast growth factors (FGF) and their receptors are involved in the paracrine modulation of ovarian function. For example, FGF2, 7 and 10 inhibit estradiol secretion by granulosa cells in vitro. Another member of this family, FGF8, is an oocyte-derived protein that modulates glycolysis in cumulus cells. FGFs are grouped into subfamilies of closely-related proteins, and FGF18 is in the same subfamily as FGF8 and has also been detected in mouse oocytes. The existance of a subfamily of FGFs that are specifically derived from the oocyte are potentially interesting paracrine regulators of fertility. The objectives of the present study were to localize the expression of FGF18 in the bovine follicle, to gain insight into the control of FGF18 expression and to identify potential actions of FGF18 in the follicle. Bovine ovaries were obtained from an abattoir for localizing expression patterns by real-time PCR and immunohistochemistry. FGF18 mRNA was not detected in pooled oocytes by PCR, but was present in isolated theca and granulosa cells (GC), and protein was detected in the follicle wall by immunohistochemistry. Expression during follicle growth was measured by collecting the two largest follicles per cow at defined stages of the first follicle wave. The follicles were classified as dominant and subordinate according to estradiol levels in follicular fluid and aromatase mRNA abundance in GC. FGF18 mRNA abundance in both GC and theca cells was higher in subordinate follicles compared with dominant follicles (P<0.05). To determine regulation and function of FGF18, granulosa cells were isolated from 5-8 mm follicles and employed in an estrogenic, serum-free culture system. In vitro, FGF18 expression was down-regulated by IGF1, insulin, FGF2, FGF10 (P<0.05) in GC. In further experiments, the addition of graded doses of FGF18 (0, 1, 10, 100 ng/ml) to GC in culture inhibited estradiol secretion and abundance of mRNA encoding the estrogenic enzymes aromatase and 17β-hydroxysteroid dehydrogenase (17βHSD), and the FSH receptor. Progesterone secretion was also inhibited, which was associated with decreased abundance of mRNA encoding CYP11, StAR and 3βHSD. Assessment of apoptosis by flow cytometry showed that FGF18 significantly increased the proportion of apoptotic cells, and this was accompanied by decreased abundance of mRNA encoding antiapoptotic and proliferation genes (MIF, RFC4 and GADD45B). In summary, FGF18 is expressed in GC and theca cells but--in contrast to the subfamily prototype, FGF8--not in oocytes in cattle. As FGF18 expression is increased in atretic follicles, and as FGF18 protein inhibits estradiol secretion and induces apoptosis, we conclude that FGF18 plays a role in follicular atresia. Supported by NSERC Canada, CNPq and FAPESP, Brazil. (platform)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".